Three-dimensional network of creatine metabolism: From intracellular energy shuttle to systemic metabolic regulatory switch.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic models without primary human trial data
PubMed 40780445 · doi:10.1016/j.molmet.2025.102228
What was done
This is a narrative review that synthesizes historical and recent advances in creatine metabolism. The authors propose a three-dimensional framework covering subcellular energy transport, the muscle-fat metabolic axis, and systemic energy sensing and metabolic reprogramming.
What was found
The abstract reports no empirical data or quantitative metrics. It describes qualitative mechanistic concepts, including mitochondrial supercomplex energy transport (VDAC/ANT-CK), creatine kinase liquid-liquid phase separation for rapid energy matching, and adipose tissue creatine cycling to stimulate brown adipocyte renewal and energy expenditure.
Why it matters
It broadens the paradigm of creatine biology from an athletic ergogenic aid and intracellular energy shuttle to a systemic regulator of whole-body energy expenditure and a potential target for metabolic disorders.
Limits
The paper is a conceptual narrative review providing no primary experimental data, statistical metrics, or systematic search methodology. Proposed clinical and therapeutic implications remain theoretical hypotheses requiring validation in controlled human trials.
Cited by
- supports In animal models, creatine has been shown to have beneficial effects on fat from a cellular perspective.